Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein C (PC) is the pivotal anticoagulant and antithrombotic in the human coagulation cascade. PC deficiency can result in major medical problems such as deep vein thrombosis (DVT), leading to tissue oxygen deprivation. PC treatment has no bleeding or skin necrosis problems because it circulates in the blood as a zymogen and is only activated when and where it is needed. One source of PC is transgenic animal milk. The major components in the milk, such as alpha-casein, beta-casein, kappa-casein, alpha-lactalbumin and beta-lactoglobulin, are proteins that must be separated from PC. Immobilized metal affinity chromatography (IMAC) is an inexpensive separation technology with relatively high specificity, and it has great potential for difficult protein separations. After systematic studies of different chelator, metal ion and buffers, the combination of iminodiacetic acid (IDA) and Fe was found to be effective to separate PC from major milk components. alpha-Lactalbumin and beta-lactoglobulin fell through the column in the starting buffer. PC was eluted. alpha-Casein, beta-casein, kappa-casein remained bound in the column after PC elution. This technology might be applied for PC separation from transgenic animal milk. It is very important for PC production in large quantities and at low cost to treat PC-deficient patients.
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PMID:Chelator, metal ion and buffer studies for protein C separation. 1206 12

Thromboangiitis obliterans (TAO) and antiphospholipid syndrome (APS) share the clinical characteristics of arterial thrombosis and recurrent thrombophlebitis. Although the association of anticardiolipin antibodies (aCLa) and TAO has been previously recognized, the prevalence and the clinical impact of this association remains unclear. aCLa were measured by double ELISA in patients with TAO (n = 47), premature atherosclerosis (pASO) (n=48) and otherwise healthy individuals (n = 48). Antibody status was then compared to clinical presentation and outcomes in patients meeting the diagnostic criteria for TAO. The prevalence of aCLa was significantly higher in patients with TAO (36%) compared to either pASO (8%; p = 0.01) or healthy individuals (2%; p < 0.001). Patients with TAO and a high antibody titer tended to be younger and suffer a significantly higher rate of major amputations compared to those without the antibody (100% versus 17%; p = 0.003). Clinical features of TAO not significantly altered by the presence of aCLa included upper limb involvement, digital necrosis, superficial thrombophlebitis (or deep venous thrombosis). Protein C, protein S, and anti-thrombin III were normal in all individuals. TAO is associated with an increased prevalence of aCLa. The presence of a high antibody titer in these patients is associated with increased morbidity, including major limb amputation. In patients meeting the diagnostic criteria for TAO, screening for aCLa should be considered. Although attractive, the efficacy of chronic anticoagulation in this setting remains to be proven.
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PMID:Antiphospholipid antibodies in thromboangiitis obliterans. 1271 Aug 39

Cancer procoagulant (CP) is a cysteine proteinase that may be produced by malignant and foetal tissue. The possible role of CP in the pathogenesis of cancer-related thrombosis has been suggested recently. The purpose of the study was to evaluate coagulation prothrombotic markers and their relation to CP concentration in the blood of patients with gastrointestinal adenocarcinomas (GIAC). The study group consisted of 45 patients with confirmed diagnosis of adenocarcinoma (stomach, 18 patients; colon, 27 patients) and without evident metastatic disease. In 24 patients further observation showed metastases. The control group for CP was composed of 10 healthy subjects. Blood samples were drawn on the admission day, before any treatment. Among 45 patients with GIAC, deep venous thrombosis was observed in two (4.4%). In all patients the CP activity in the serum was found, and the mean CP activity shortened the coagulation time almost three times compared with the healthy control group. Also, the mean thrombin-antithrombin complex concentration was above the normal range. A significant elevation of the mean prothrombin fragment 1+2 plasma content in this group of patients was noticed. Despite these observations, CP remained within the normal range and did not correlate with thrombin-antithrombin complex or prothrombin fragment 1+2 plasma concentrations. A positive correlation was observed between serum CP and fibrinogen concentration, and a negative correlation between CP and free protein S plasma content (P = 0.04 and P = 0.025, respectively). A negative correlation between activated protein C resistance ratio and protein C activity in the plasma was confirmed. Protein C activity in the plasma showed a correlation with free protein S plasma content. Analysis of factors influencing the activated partial thromboplastin time revealed the presence of antiphospholipid antibodies in seven persons from the study group (in three cases of IgG and in four cases of IgM class). Our data suggest that CP is a minor risk factor for deep venous thrombosis in GIAC patients. To confirm this, however, the number of patients and controls should be larger. After 3 years of observation, the follow-up in 10 living GIAC patients showed nobody with thromboembolic disease.
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PMID:Cancer procoagulant in patients with adenocarcinomas. 1626 26

Protein C (PC) is the pivotal anticoagulant and antithrombotic in the human coagulation cascade. PC deficiency can disturb the blood hemostasis and cause thrombosis, inhibiting oxygen transport to tissue, and resulting in major medical problems such as deep vein thrombosis (DVT). The current treatment can cause bleeding and other major medical problems. PC circulates in the blood as a zymogen and is only activated when and where it is needed. PC is a safe anticoagulant without harmful side effects. A combination of ion-exchange chromatography and IMAC IDA-Cu was studied for the relatively large scaled PC separation from Cohn fraction IV-1. Almost half of the active PC was recovered by using this process. In future work, we will verify the linearity of the IMAC column scale-up. This process can be used to produce PC from Cohn fraction IV-1 at large quantities and low cost to treat PC-deficient patients.
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PMID:Process scale-up studies for protein C separation using IMAC. 1659 58

Protein C is an important blood factor protein that regulates the blood coagulation process. Deficiency of protein C can lead to excessive coagulation that results in lack of tissue oxygenation, causing conditions such as deep vein thrombosis, pulmonary embolism, and stroke. Human protein C has been approved as a treatment for congenital protein C deficiency; however, the therapy requires frequent injections, due to the short residence time of the protein. Subcutaneous administration has been examined as an alternative to increase residence time and decrease injection frequency, thereby creating a more patient-friendly dosing regimen. In order to design an efficient injection or infusion protocol for subcutaneously administered proteins, it is important to accurately model the behavior (absorption, distribution, elimination) of these proteins in the body. However, several factors involved in a subcutaneous injection of the protein make modeling this behavior a challenging task. For example, absorption of the drug from the subcutaneous site into the blood stream can be variable depending on the site of injection, physical activity of the patient, etc. Furthermore, degradation of the protein can occur at the site of injection and further modify its absorption. The objective of this work was to demonstrate the utility of frequency response modeling as an alternative method to analyze the behavior of subcutaneously administered protein C. The results of our study indicate that if the dose range yielding the constant clearance of protein C is identified for the patient, models of that type, as presented in our study, can be used to adjust optimal dosing of protein C necessary to reach prescribed levels of the protein in this patient at desired time points, both specified by treatment requirements.
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PMID:Modeling behavior of protein C during and after subcutaneous administration. 1659 77

Pulmonary hypertension in pregnancy is a rare condition but is associated with a high mortality. We report the case of a 29 year old female in early pregnancy with Protein C and S deficiency with recurrent deep venous thrombosis and pulmonary embolism and subsequent secondary pulmonary hypertension. The patient was counselled and consented for termination of pregnancy with tubal sterilization. She was administered continuous spinal anaesthesia with invasive monitoring. The successful anaesthetic management of this condition is described.
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PMID:Technique of anaesthesia in pulmonary hypertension and thrombophilia in early pregnancy. 1670 49

Anti-coagulant proteins are essential to maintain blood hemostatis for the supply of oxygen and nutrients to tissue cells and for the removal of toxic by-products from metabolism. Hereditary or acquired deficiencies of Protein C, Protein S, or Antithrombin III can lead to disease states such as deep vein thrombosis (DVT) with the possibility of producing lung emboli. Phenomena named Factor V Lieden can produce a similar pathologic condition. Anti-coagulant deficiencies, including Factor V Lieden, are HIDDEN blood conditions that can allow blood clot development, especially with trauma to the tissue and circulatory system. It is proposed that all children between ages twelve to fourteen be checked hereditary deficiencies and Factor V Lieden complications. This would require the development of inexpensive assay equipment12. The present research focuses on the low cost production of Zymogen Protein C via purification from blood plasma Cohn Fraction IV-1. This process is difficult due to the several Homologous Vitamin K dependent proteins in the blood coagulation cascade. Traditional chromatography (ion exchange) cannot achieve the desired separation. Some more exotic technologies are very expensive so our work proposes to use Immobilized Metal Affinity Chromatography (IMAC). It is hoped to produce a lower cost product that can be used prophylactic ally to treat Protein C deficiencies and possibly other coagulation problems.
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PMID:Anticoagulant blood factor deficiencies (protein C). 1772 40

Several inherited polymorphisms are associated with risk of venous thrombosis, including mutation at codon 506 of the factor V gene, mutation at position 20210 of the prothrombin gene, and mutations in the protein C gene. In this study, genotyping for factor V, prothrombin, and protein C mutations was performed in 50 patients and 25 control subjects by polymerase chain reaction-based analysis. The prevalence of factor V and prothrombin mutations was not significantly different from that in the general population. Nine of the patients had heterozygous protein C mutation. There was a high prevalence of the mutated protein C allele in the pulmonary emboli group (42.8%). Protein C mutation incidence was higher in the pulmonary emboli group than in the deep vein thrombosis (8.33%) and cerebral vein thrombosis (16.1%) groups. These results indicate that patients with protein C deficiency have a greater risk of thrombosis than patients with factor V or prothrombin G20210A mutation.
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PMID:Factor V Leiden, prothrombin G20210A, and protein C mutation frequency in Turkish venous thrombosis patients. 1816 Jun 1

Thrombin generation measurement may be of value for assessing the risk of venous thromboembolism, but its long term profile has not been assessed in patients. We evaluated thrombin generation by Calibrated Automated Thrombogram (CAT) in plasma during follow up of 104 consecutive patients after an acute episode of deep venous thrombosis. Blood was drawn three times over the course of 24 months. Thrombin generation was measured in absence and presence of thrombomodulin and compared to a reference range derived from thrombin generation curves in 137 healthy volunteers. Thrombin generation of patients showed significantly higher endogenous thrombin potential (ETP) and peak height compared to the reference population. Differences were more pronounced in assays triggered with 1 pM TF. Inhibition by thrombomodulin was attenuated in patients off anticoagulants as compared to the reference population (21% vs. 42.2%, p < 0.0001); inhibition in patients on anticoagulant treatment was less pronounced (9.7%, p < 0.0001). Protein C activity, protein S antigen as well as free protein S showed highly negative correlation with ETP in all patients. A significant negative relation was found between FVIII levels and thrombomodulin induced reduction of ETP and peak height. In conclusion, thrombin generation by CAT reflects changes in coagulation status in patients following a thromboembolic event and is most sensitive at CAT analysis triggered with 1 pM TF. A role for factor VIII as an important attributable cause of hypercoagulability is reflected by the reduced inhibitory effect of thrombomodulin at high factor VIII levels.
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PMID:Thrombin generation in patients after acute deep-vein thrombosis. 1869 Mar 43

Microparticles (MPs) are blebs released from cellular surfaces during activation/apoptosis. They are procoagulant, pro-inflammatory and could contribute to pathogenesis of deep venous thrombosis (DVT). This study compared the number, cellular origin and procoagulant activity of MPs on DVT patients in different clinical situations: at diagnosis (n = 9, 5F/4M; mean age = 41.11), 1-3 years after warfarin withdrawal (n = 10, 7F/3M; mean age = 32.90), associated to antiphospholipid syndrome (APS; n = 11, 9F/2M; mean age = 33.82), or asymptomatic carriers of Factor V Leiden (FVL; n = 7, 7F/0M; mean age = 34.00) vs healthy controls (CTR). The quantification and characterization were performed by flow cytometry using CD235, CD61, CD45, CD31, CD14, CD45, anti-TF and Annexin V. The plasmatic procoagulant activity was investigated by prothrombin fragment 1 + 2 (F1 + 2) determination. The MPs procoagulant activity was analyzed by D-dimer (DD2) and Thrombin Generation Test (TGT) on a healthy pool of plasmas adjusted or not by their number (10,000 MPs). The MPs percentages were not different between the groups, but absolute number was increased in patients 1-3 years after warfarin withdrawal vs CTR (P = 0.02). There was no difference of the MPs cellular origin comparing patients to controls. TGT using 10,000 MPs was lower on these patients (P = 0.01). APS patients showed a reduction of plasmatic procoagulant activity (P = 0.004), but they were under warfarin therapy. DD2 in the presence of MPs, independently of its number, was higher in patients with DVT at diagnosis (P < 0.0001). MPs of patients with spontaneous DVT at diagnosis can promote coagulation activation demonstrated by increased DD2. Even the increased MPs from patients 1-3 years after thrombotic episode generated lower amount of thrombin, they can have a protective effect by activation of Protein C anticoagulant pathway.
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PMID:Microparticles in deep venous thrombosis, antiphospholipid syndrome and Factor V Leiden. 1981 Dec 20


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